Beta-adrenergic agonists are used in the treatment of chronic and exercise- induced asthma. These agents work through the beta adrenergic receptor/adenylate cyclase coupled effector system producing relaxation of the smooth muscle of the trachea and bronchial tree thereby relieving asthmatic symptoms. Agonist binding by the receptor leads to a desensitization and reduced agonist response. A novel protein kinase, beta adrenergic receptor kinase, is intimately involved in this process. The aim of this proposal is to establish the means of identifying specific inhibitors of this kinase which could be used to extend the effectiveness of beta agonists. Specifically, a range of available human cells and tissues will be screened as potential sources of the kinase and then it will be purified from the best source. Candidate peptides will be prepared and examined as model substrates for the kinase. The components will then be configured to a high throughput assay designed to identify potential drugs. In phase II we will clone and express the kinase, if this is required, and initiate screening. We will also establish secondary screens designed to evaluate the specificity and in vivo effectiveness of lead compounds from the primary high throughput screen.